KR101744339B1 - Surface Acoustic Wave Sensor Device Including Target Biomolecule Isolation Component - Google Patents

Abstract

The present invention relates to a surface acoustic wave sensor device including a separation element of a target biomolecule, wherein a sample containing a target biomolecule is separated in size through electrophoresis, and then sequentially reacted with the SAW sensor. That is, biomolecules are separated using electrophoresis, and then separated biomolecules are applied to a SAW sensor to detect target biomolecules.

Description

[0001] The present invention relates to a surface acoustic wave sensor device including a separation element of a target biomolecule,

A surface acoustic wave sensor device including a separation element of a target biomolecule, and a detection method of the target biomolecule.

Surface Acoustic Wave (SAW) is a mechanical wave generated from the movement of particles by external thermal, mechanical, and electrical forces, not by electromagnetic waves. Most of the vibration energy is concentrated on the surface of the medium. The SAW sensor is a device for sensing the presence or physical properties of a target material by using a surface acoustic wave.

The SAW sensor is formed on a substrate made of a piezoelectric material, and a receptor having a specific binding with a desired target material is attached to the sensor surface. Thus, when the solution containing the target material is flowed into the SAW sensor, the wavelength is changed by the physical, chemical, and electrical reaction between the target material and the receptor, and the content of the target material is diagnosed and monitored through the signal change .

In the case of a biosensor, biosensors such as proteins, DNA, viruses, bacteria, animal cells, tissues and toxins generated by the biosensors are detected. Biomolecules, etc. specifically bind to the surface of the sensor, which changes the surface mass of the sensor, which causes a signal change in the sensor. Here, the sensor is very sensitive to not only the mass change of the surface but also the pressure of the fluid and the viscosity and density of the medium.

The resonance and oscillation device for making the SAW device wave can be obtained by oscillating the output signal from the SAW device into the input signal of the SAW device again to observe the wave change of the SAW device, There is a method of measuring the change of the output signal applied to the input IDT of the SAW device by plotting the output signal according to each frequency.

According to an aspect of the present invention, there is provided a biosensor comprising (i) a biomolecule having the same or similar size as the target biomolecule, or (ii) a biomolecule having a size significantly different from that of the target biomolecule, There is disclosed a surface acoustic wave sensor device including a SAW sensor having a receptor that specifically binds to a molecule.

The electrophoresis is not particularly limited as long as the biomolecule can be separated according to its size. Examples of the electrophoresis include gel electrophoresis, capillary electrophoresis, isoelectric focusing electrophoresis, and isotachophoresis. have.

In one example, the separation element includes a first chamber containing a first buffer solution and containing a first chamber and a second buffer solution, the second chamber containing a second electrode, the first chamber and the second chamber, A blocking chamber formed at a channel side end of at least one of the first chamber and the second chamber, a sample chamber located at an inlet side of the channel and to which a sample is loaded, and a channel located at an outlet side of the channel, And the SAW sensor is connected to the third chamber.

The channels may be one or a plurality of gel tubes filled with gel for migration, or may be capillaries. In the case of a plurality of channels, the plurality of channels may be the same or different from each other, and examples of the latter may be selected from the group consisting of sample type, channel size, channel length, gel component, gel concentration, These are the different channels.

The SAW sensor may further include an upper channel and a lower channel formed at upper and lower ends of the third chamber, and the waste chamber may be located in the upper channel. A pump may be located at the end of the upper channel and / or the lower channel.

The SAW sensor includes a piezoelectric substrate, a pair of IDTs (Inter-Digital Transducer) electrodes formed on the substrate, and a plurality of IDT electrodes formed on the piezoelectric substrate to cover the IDT electrodes, And the like.

An electrical sensor for sensing biomolecules may be located in the third chamber.

The blocking wall may be made of a material that allows current to pass therethrough but does not allow ions and / or gases generated from the buffer solution to pass therethrough.

According to another aspect, there is provided a method for separating a biomolecule having the same or similar size as a target biomolecule from a sample, or separating a biomolecule other than a biomolecule having a size significantly different from that of the target biomolecule, Reacting the target biomolecule with a reaction portion of a surface of a SAW sensor having a receptor that specifically binds to a target biomolecule.

The step of separating the biomolecules may be performed by an electrophoresis method.

Detection of such a target biomolecule can be performed using the SAW sensor device described above.

1 is a schematic view of a surface acoustic wave sensor according to an embodiment of the present invention;
2 is a schematic view of a surface acoustic wave sensor according to another embodiment of the present invention;
3 is a schematic diagram of a detection process when target biomolecules are relatively small in size;
Figure 4 is a schematic diagram of the detection process when the target biomolecule is relatively large;
5 is a schematic diagram of a SAW sensor according to an example of the present invention.

Hereinafter, advantages and features of the present invention and methods of performing the same will be more readily understood by reference to the following detailed description of the embodiments and the accompanying drawings. However, it should be understood that the present invention may be embodied in many other specific forms without departing from the spirit or scope of the invention.

Surface acoustic wave sensor device

In one example, a surface acoustic wave sensor device capable of detecting a target biomolecule using a surface acoustic wave sensor is provided. A surface acoustic wave sensor (hereinafter also referred to as a SAW sensor) fixes a receptor that specifically binds to a specific target biomolecule on its surface and detects an increased surface when the target biomolecule existing in the sample binds to the receptor The velocity of the surface wave is inhibited by the mass density, and qualitative and quantitative analysis of the target biomolecules is performed through the change of the velocity.

However, when a substance other than the target biomolecule in the sample is non-specifically bound to the surface of the SAW sensor, there is a problem that the surface acoustic wave velocity changes and acts as noise in the detection process. For example, the blood mainly used as a sample contains a large amount of antibody used as a receptor, and if it is not separated in advance, the reaction between the receptor antibody on the surface of the SAW sensor and the target biomolecule is inhibited. In addition to the antibody, when the amount of other substances such as protein is large in the sample, the diffusion of the target biomolecule is disturbed and the binding rate with the SAW surface receptor is inhibited.

To solve this problem, a method of separating a target biomolecule using an affinity column using an antibody can be used. However, this method requires the use of a solution that lowers the affinity of the antibody by lowering the pH or changing the concentration of the ion for re-separation with antibodies immobilized on the column. This also has the problem of reducing the sensitivity of the separated target biomolecules by interfering with the binding force of the antibody on the surface of the SAW sensor.

Accordingly, there is provided a sensor device capable of separating a target biomolecule in a sample from a large amount of other substances by applying an electrophoresis method to the SAW sensor. Electrophoresis utilizes the principle that electrons move in a constant direction and speed depending on their charge and mobility when an electric field is applied to an ionic substance. It is a technology that is separated by the mobility difference according to the surface charge characteristic according to the size, shape and the average charge amount of the ionic substance and the pH, concentration and temperature of the aqueous solution. According to this, the size of the biomolecule and the mobility in the electric field are inversely proportional to the logarithmic function. Therefore, since the biomolecule can be separated purely according to its size, no subsequent process is required.

According to one example, as a sensor for detecting a target biomolecule in a sample, a biomolecule having the same or similar size as the target biomolecule or a biomolecule having a size significantly different from that of the target biomolecule is separated And a SAW sensor attached with a receptor that specifically binds to the target biomolecule are integrated into the surface acoustic wave sensor device. That is, various biomolecules in the sample can be separated by size primarily through the electrophoresis apparatus, and biomolecules that are separated secondarily, that is, biomolecules having substantially the same size as the target biomolecules or having no significant size difference The target biomolecule can be detected by the SAW sensor on molecules.

The separation by electrophoresis is caused by the difference in the migration speed depending on the nature of the particles such as the structure and size of the different sample components in the electric field.

In a gel electrophoresis, a sample or a sample can be moved between them by using a membrane or a gel as a support. Examples of the support include filter paper, cellulose acetate, agarose gel, starch gel, acrylamide gel and the like.

Filter paper is a cheap and easy to use support. However, the boundaries between the strips of electrophoresis are not clear because the substances to be separated are adsorbed well on the cellulose.

Acetic acid cellulose is acetylated hydroxy group of cellulose acetate and has a short separation time, is easy to be detected and easily dissolves in various solvents and can be recovered quickly and easily.

Because agarose gel is transparent, it is suitable for measurement using a photometer and is easy to use. Agarose, which is widely used for immunoelectrophoresis using slides and has agaropectin removed from agar gel, is useful for isolating DNA, RNA and plasmids.

The size of the pores of the starch gel is determined by the type of starch, the type of buffer solution and the pH, and serves as a sieve for molecular sieving. It is widely used for the isolation of several isoenzymes.

The acrylamide gels are used to form a discontinuous layer by superimposing two acrylamide gels having different netting structures. In this case, the size of the hole of the mesh structure of the support body can be arbitrarily changed by changing the concentration of acrylamide. The less dense gel in the upper layer is a stacking gel that serves to concentrate charged particles such as protein, so that the sample passing through this part forms a distinct time. Acrylamide gels are not only able to separate according to the charge of the components, but also can be separated by mass depending on the mass. Separation of proteins, determination of purity of purified proteins, measurement of molecular weight of proteins, and determination of the order of base binding of DNA. There is an advantage that the sample mixture can be separated in a short time using a small amount of the sample.

The use of a gel as a support in the above is referred to as gel electrophoresis. On the other side, if the sample is in band, it is called band electrophoresis. Molecules with the same size form a group and move. When they are electrophoresis, they appear as a band. As small molecules move at a faster rate than large molecules, the result is that molecules of different sizes are banded at different positions on the gel. The size of the molecules that make up each band can be measured by comparing the size of the band on the gel by electrophoresis of molecules of known size.

There is also disc electrophoresis. Discontinuous electrophoresis is a modification of the band electrophoresis method using acrylamide gel so that the charged lobules, such as proteins, can be separated into very distinct strips. The difference from the band electrophoresis method is that two gels are used and that the gel supports and buffer systems used in the buffer solution tank are different. This electrophoresis method is called discontinuous gel electrophoresis because the concentration of hydrogen ions, the intensity of ions, the composition of buffer solution and the gel concentration used in the two gel systems are discontinuous. Such acrylamide electrophoresis can distinguish one base pair difference due to its high resolution, can handle a large amount of sample, and can easily recover the sample material from the gel.

In addition to gel electrophoresis, electrophoresis may include capillary electrophoresis, isoelectric focusing electrophoresis, and isotachophoresis.

In the case of capillary electrophoresis (capillary electrophoresis), the capillary separates according to the size of the molecule and can be measured using a detector. The capillary electrophoresis method utilizes a capillary with an inner diameter of 25-75 ㎛. Electr oto omotic flow, which is an electrophoretic phenomenon, achieves efficiency as high as over 100,000 theoretical. Capillary electrophoresis has the advantage of simultaneously analyzing all solutes, regardless of their high efficiency, fast assay time, low sample requirements and charge. Therefore, it is widely used for the analysis of biological macromolecules, amino acids, chiral drugs, proteins, carbohydrates and the like. The capillary walls are modified or coated with an inactive material such as polyacrylamide, poly (vinyl-pyrrolidone), and the like.

The isoelectric focusing electrophoresis utilizes that the charged component (e.g., protein) is focused at a specific location in the support material. The amino acid, a component of the protein, has a specific charge on each residue in the aqueous solution. Therefore, proteins that are polymers of these amino acids also have charges derived from these amino acids. These charges change as the pH of the aqueous solution changes. Positive charge is neutral, or negative charge is neutral. Therefore, when these protein mixtures are placed on a gel with a pH gradient and an electric field is applied, they move to opposite charges due to their charge. As they move, the pH changes, In the neutral charge position, since the net charge is zero, it stops moving and stops. IEF uses this principle to separate proteins by isoelectric point.

The isotachophoresis is slightly different from other electrophoresis techniques in that there is no support material for removing the convective current in the electrolyte. Instead, diffusion is reduced as separation is performed in the capillary. Moreover, the dilution effects caused by the electrophoretic migration of buffer ions through the sample compartments are eliminated by using two buffer ions that are very different from each other. The buffer at the front contains ions that move faster than the sample ions, while the buffer at the back contains ions that move slower than the sample ions so that no disturbance of the sample ions by the buffer ions occurs. Each zone is detected by a potential gradient detector that is sensitive to local changes in the electric field as it passes through the ultraviolet absorption or sample zone systems. This technique may be widely applied to small organic ions and inorganic ions, for example the minerals in the effluent of (NO ^3-, SO ₄ ^2-) or an amino acid, wine, fruit juice, an organic acid in a physiological sample.

However, when the conventional electrophoresis apparatus is applied as it is, sample biomolecules sampled or separated by the buffer solution for current transfer can be diluted.

Thus, in the example of the present invention, the buffer chamber and the sample chamber are separated to protect the sample from ions generated in the buffer chamber upon application of electric current without diluting the sample itself or diluting the separated target biomolecule.

1 and 2 schematically show a SAW sensor device according to an example of the present invention.

1, a channel 30 is formed between the first chamber 10 and the second chamber 20, which constitutes an electrophoresis apparatus, and detects a target biomolecule from a sample subjected to electrophoresis The SAW sensor 100 is included.

Such a sensor device primarily separates a biomolecule having a size similar to that of the target biomolecule from the sample through electrophoresis or separates biomolecules having a size significantly different from that of the target biomolecule. Then, the biomolecules are transferred to the SAW sensor. In the former case, the separated biomolecules are transferred to the SAW sensor 100, and in the latter case, the biomolecules other than the separated biomolecules are transferred to the SAW sensor 100.

Accordingly, it is possible to reduce errors due to non-specific coupling in the SAW sensor 100, to increase the sensitivity and reproducibility, and to remove the large amount of reaction dirt (Antibody, etc.) in the sample to improve the reaction speed on the surface of the SAW sensor, The sensitivity can be improved. In addition, by using an electrophoresis method for separating target biomolecules, pure sample separation can be performed without damaging the sample due to separation, and the cost is low because no expensive antibody is used. In addition, since the re-separation process of the target biomolecule is not required in the subsequent process after the separation, there is no sensitivity loss at the time of SAW sensing, so that it is possible to have a high sensitivity and to separate the process easily and quickly.

The first chamber 10 and the second chamber 20 contain the first buffer solution and the second buffer solution, respectively, and the first electrode 11 and the second electrode 21 are contained.

The channel (30) connects between the first and second chambers (20). The channel 30 may be a gel tube filled with a gel for gel filtration, or may be a capillary. Capillaries include those that are filled with or not filled with a gel for gel filtration. The component of the gel or the size of the capillary may be selected depending on the type of the target biomolecule. Agarose gel, starch gel, acrylamide gel and the like can be used as the gel for the gel, and agarose gel is mainly used for the DNA or RNA, polyacrylamide is used for the protein, The gel is mainly used.

The number of the channels 30 may be one or plural, and the plurality of the channels 30 may be the same or different. In the case where the plurality of channels 30 are different from each other, for example, the kind of the sample, the size of the channel 30, the length of the channel 30, the component (kind) One or more selected from the coating materials of the channel 30 may be made different from each other. A different kind of sample means that the sample flowing into each channel 30 is different. When the channel 30 is a capillary, characteristics such as capillary size, inner coating, length, etc. may be configured differently, or the gel may have different components when the gel is filled therein. The plurality of channels 30 may be included in the form of an array or a cartridge.

Between the first chamber 10 and the channel 30, which is the inlet side of the channel 30, there is a sample chamber 60 in which a sample is loaded. A third chamber 70 through which the biomolecules passing through the channel 30 are transferred is provided between the channel 30 and the second chamber 20 at the outlet of the channel 30. Thus, when a sample is loaded into the sample chamber 60 and electric power is supplied, the biomolecules in the sample move to the channel 30. In addition, the biomolecules passing through the channel 30 move to the third chamber 70.

At the end of the first chamber 10 or the second chamber 20 on the side of the channel 30, blocking walls 40 and 50 for blocking the flow of the buffer solution from the buffer chambers 10 and 20 are formed . The blocking wall is for preventing the dilution of the sample sample and is formed at least at the side of the channel 30 side in the second chamber 20 so that the sample sample diluted with the SAW sensor 100 is not introduced, As shown in Fig. That is, a first blocking wall 40 is formed to separate the sample chamber 60 from the buffer chamber (the first chamber 10), and a third chamber (not shown) through which the biomolecules passing through the channel 30 are transported 70 and the buffer chamber (second chamber 20). By forming the blocking walls 40 and 50 in this way, the buffer solution can prevent the dilution of the sample itself or dilution of the target biomolecules separated. In addition, the sample can be protected from ions generated in the buffer chamber upon application of current for electrophoresis.

The blocking walls 40 and 50 may be those having current passing therethrough but not passing ions and / or gas arising from the buffer solution. For example, electricity, but not hydrogen ions and hydroxide ions and / or gases. Specifically, the barrier walls 40 and 50 may include, but are not limited to, Nafion ^™ (Dupont), Dowex ^™ (Aldrich), and Diaion ^™ (Aldrich).

In this structure, an electric field is formed by the electrodes 11 and 21 located on both sides of the channel 30. The charged particles pass through the channel 30, which is a medium in the electric field, Respectively. The process of separating biomolecules will be exemplified. When a voltage is applied to both electrodes with the first buffer solution as a positive electrode and the second buffer solution as a negative electrode, a voltage difference is generated between the both buffer solutions through the gel or capillary of the channel 30. [ Due to this voltage difference, a substance positively charged in the sample is moved in the direction of the second buffer solution which surrounds the cathode, and a substance having negative charge moves in the opposite direction. At this time, each biomolecule in the sample sample is separated from each other because the moving speed of the substance varies depending on characteristics such as molecular weight and the like.

Through this electrophoresis, the biomolecules capable of interfering with binding of the target biomolecules to the surface receptor of the SAW sensor 100 are separated from the sample in advance to enhance the detection sensitivity of the SAW sensor 100.

In one example, if the size of the receptor and the target biomolecule are significantly different and biomolecules having a size similar to that of the receptor are included in the sample, they can be separated and removed. Alternatively, biomolecules other than biomolecules having a size that is significantly different from the target biomolecules can be transferred to the SAW sensor. For example, biomolecules having a size of about ± 500%, ± 400%, ± 300%, ± 200%, or ± 100% relative to the size of the target biomolecule may not be transferred to the SAW sensor, .

In another example, biomolecules having a size similar to that of the target biomolecule may be separated and transferred to the SAW sensor. For example, only biomolecules having a size of about ± 50%, ± 40%, ± 30%, ± 20%, or ± 10% of the size of the target biomolecule can be transferred to the SAW sensor device, .

The biomolecules of the target biomolecules that are significantly different in size and size from the third chamber 70 should not be transferred to the SAW sensor 100 and should be discarded. 1 and 2, the waste chamber 90 may be connected to the third chamber 70 in a direction in which the SAW sensor 100 is not connected. For example, the third chamber 70 and the waste chamber 90 are connected to the upper channel 81, the third chamber 70 and the SAW sensor are connected to the lower channel 82, respectively. Removed biomolecules move to the waste chamber 90, for example, biomolecules other than biomolecules having a size similar to that of a target biomolecule and a target biomolecule, or biomolecules having a remarkably different size are moved.

The third chamber 70 is connected to the SAW sensor 100. When the biomolecule reaches the third chamber 70, it is required to detect whether the biomolecule reaches the SAW device 100 or the waste chamber 90. Accordingly, an electric sensor (not shown) . The electric sensors may be one or more. The electric sensor may be formed only on the surface facing the channel 30, for example, and on the surface facing the upper channel 81 and the surface facing the lower channel 82, respectively.

Pumps (301, 302) are mounted on the upper channel (81) and / or the lower channel (82) to provide a transfer force for movement of biomolecules. The pumps 301 and 302 pressurize or depressurize the pressure depending on the type of the positive pressure / negative pressure.

FIGS. 3 and 4 schematically show a process of detecting a target biomolecule using a SAW sensor according to an example of the present invention. In these drawings, the elements corresponding to those in Fig. 1 omit the leader line and the indicating sign.

First, referring to FIGS. 1 and 3, a detection process is performed when a target biomolecule is relatively small in size. A sample containing the target biomolecule 200 is loaded into the sample chamber 60 and the buffer solution is filled in the first and second buffer chambers 10 and 20 (S1). When a current is supplied through the electrodes 11 and 21 in the first and second buffer chambers 10 and 20, separation is performed according to the size in the channel 31 by electrophoresis (S2). When a sample corresponding to the size of the target biomolecule 200 arrives at the third chamber 70, the biomolecule 200 moves to the other end of the channel 30, (S3). The isolated sample is moved to the SAW sensor 100 through the lower channel 82 (S4). A target receptor 300 is coupled to the surface of the SAW sensor 100.

1 and 4, the operation of the sensor for detecting a large target biomolecule is schematically shown. Unlike FIG. 3, when the biomolecules having a small size reach the third chamber 70, the current is blocked (S2) and moved to the upper channel 81 (S3). When the large-sized target biomolecules 200 reach the third chamber 70 after the small-sized biomolecules are removed and the current is applied again, the current is shut off and the SAW sensor 100 (S4).

The SAW sensor 100 can detect changes in minute mass caused by intermolecular interaction on the surface of the sensor by changing the frequency (frequency shift, phase shift, etc.).

The SAW sensor 100 can be used to detect all materials with a mass and the receptor material 300 specifically binds on the sensor surface to change the surface mass of the sensor which causes a signal change in the sensor, And the content and the content of the compound can be diagnosed.

FIG. 5 schematically shows a SAW sensor 100 according to an example of the present invention. Referring to FIG. 5, the SAW sensor 100 includes a piezoelectric substrate 110; A pair of IDTs (Inter-Digital Transducer) electrodes 121 and 122 formed on the substrate; And a reaction film 130 formed on the piezoelectric substrate 110 to cover the IDT electrodes 121 and 122 and coupled to a receptor (see 300 in FIG. 2) Lt; / RTI >

The receptor 300 is a substance that specifically binds to a target biomolecule. For example, antibodies and the like can be mentioned.

The piezoelectric material constituting the substrate 110 is a material in which electrical characteristics are changed (piezoelectric effect) when a mechanical signal is applied or a mechanical signal is generated (reverse piezoelectric effect) when an electrical signal is applied. For example, lithium niobate (eg; LiNbO _3), lithium tantalate (eg; LiTaO _3), sabung dissipation lithium _{(Li 2 B 4 O 7)} , barium titanate _{(BaTiO 3), PbZrO 3,} PbTiO 3, PZT , ZnO, GaAs, quartz, niobate, and the like.

Substrate 110 may be surface treated with a material capable of engaging the receptor to join the receptor, a material capable of forming a self-assembled monolayer (SAM), and the like.

The IDT electrode 120 is an interface between an electric circuit and an acoustic delay line. The IDT electrodes 120 may include a pair of IDT electrodes 121 and 122. One IDT 121 in the pair of IDTs 121 and 122 generates a surface acoustic wave by an applied signal and is called an input IDT 121 or a transmitter . At this time, the generated surface acoustic wave is transmitted to the other IDT 122 by expansion and compression at an appropriate frequency along the surface of the substrate, and is converted into an electrical signal by an inverse piezoelectric effect. This second IDT is referred to as an 'output IDT 122' or a 'receiver'.

The IDT electrode 120 may be made of aluminum or an aluminum alloy. The aluminum alloy may contain at least one of Ti, Si, Cr, W, Fe, Ni, Co, Pb, Nb, Ta, Zn and V with Al as a main component.

The driving principle of the SAW sensor 100 will be described in detail. An electrical signal passes through the input IDT electrode 121 to generate a mechanical wave. This wave is changed by physical, chemical, and electrical reactions by combining the receptor and the substance contained in the reaction film 130 on the surface of the SAW sensor. That is, the center frequency, phase, or signal size of the output signal of the SAW sensor 100 is changed. By observing the change of the signal, it is possible to detect that the target biomolecule 200 is coupled to the SAW sensor, and furthermore, the target substance can be analyzed qualitatively and quantitatively.

The receptor 200 is coupled to the reaction membrane 130 and the shear rate of the SAW excited by the IDT 121 changes when the weight of the target biomolecule 200 is coupled by the selective binding reaction, It is possible to precisely detect the change in the oscillation frequency as the IDT 122 used for reception measures it.

target  Method for detecting biomolecules

A method for detecting a target biomolecule among various biomolecules present in a sample is provided.

In one example, separating a biomolecule having the same or similar size as a target biomolecule from a sample, or separating a biomolecule other than a biomolecule having a size significantly different from that of the target biomolecule, To a reaction part of a SAW sensor surface to which a receptor specifically binding to a target biomolecule is attached.

According to this method, various biomolecules existing in the sample are firstly separated according to their sizes, and biomolecules having a size substantially similar to that of the target biomolecules or biomolecules other than biomolecules having a remarkable size difference from the target biomolecules And detects whether or not the reaction with the receptor is performed by the SAW sensor. Therefore, it is possible to reduce errors due to nonspecific binding, increase sensitivity and reproducibility, and improve response speed on SAW sensor device surface by removing a large amount of reaction dirt (Antibody, etc.) in the sample to improve sensitivity .

The step of separating the biomolecules by size may be performed by an electrophoresis method. It is necessary to prevent the sample from being diluted by the buffer solution or denatured by the pH change due to the current inflow in the process of separating biomolecules through the electrophoresis method. Therefore, the above-described SAW sensor can be used.

The separated biomolecules are similar in size to the target biomolecules. For example, the separated biomolecules have a size of about ± 50%, ± 40%, ± 30%, ± 20%, or ± 10% Lt; / RTI >

The separated biomolecules may be excluded from the biomolecules that have a significant difference in size compared to the size of the target biomolecule. For example, biomolecules other than biomolecules having a size of about ± 500%, ± 400%, ± 300%, ± 200%, or ± 100% of the size of the target biomolecule.

Those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims (10)

A second chamber including a first electrode, a first electrode and a first buffer solution, a second electrode including a second electrode and a second buffer solution, a channel connecting the first chamber and the second chamber, A separation chamber for separating the target biomolecule by using an electrophoresis method, the separation chamber comprising: a sample chamber which is located at an outlet side of the channel and through which a biomolecule passed through the channel passes; And
And a surface acoustic wave ('SAW') sensor having a receptor that specifically binds to the target biomolecule. The method according to claim 1,
Wherein the electrophoresis is selected from the group consisting of gel electrophoresis, capillary electrophoresis, isoelectric focusing electrophoresis, and isotachophoresis. delete The method according to claim 1,
An upper channel having a waste chamber disposed at upper and lower ends of the third chamber, and a lower channel having a SAW sensor disposed thereon, and a pump is disposed at an end of at least one of the upper channel and the lower channel. The method according to claim 1,
Wherein the channel is one or a plurality of gel tubes filled with a gel for migration or capillary. 6. The method of claim 5,
Wherein the at least one selected from the type of the sample, the size of the channel, the length of the channel, the composition of the gel, the concentration of the gel, and the coating material of the channel comprise different channels. The method according to claim 1,
And an electric sensor for sensing biomolecules is located in the third chamber. delete delete delete

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